Functionalization unfunctionalized alkenes

Enantioselective epoxidation of unfunctionalized alkenes was until recently limited to certain ds-alkenes, but most types of alkenes can now be successfully epoxi-dized with sugar-derived dioxiranes (see Section 9.1.1.1) [2]. Selective monoepox-idation of dienes has thus become a fast route to vinylepoxides. Functionalized dienes, such as dienones, can be epoxidized with excellent enantioselectivities (see Section 9.1.2). 

The protocol developed by Jacobsen and Katsuki for the salen-Mn catalyzed asymmetric epoxidation of unfunctionalized alkenes continues to dominate the field. The mechanism of the oxygen transfer has not yet been fully elucidated, although recent molecular orbital calculations based on density functional theory suggest a radical intermediate (2), whose stability and lifetime dictate the degree of cis/trans isomerization during the epoxidation <00AG(E)589>. 

Although there are many reports on the enantioselective catalytic double bond isomerization of functionalized achiral alkenes, that of alkenes bearing an isolated double bond have had limited success. The use of a chiral bis(indenyl)titanium catalyst 5 containing a chiral bridging group realized the highly enantioselective isomerizations of unfunctionalized achiral alkenes with up to 80% ee (Equation (27)).90... 

Finally, the phosphinite-oxazole catalyst 29 (Fig. 29.16) was recently reported and used to hydrogenate a series of functionalized and unfunctionalized alkenes [31]. It was anticipated that the planar oxazole unit and the fused ring system would improve the enantioselectivity compared to the PHOX catalyst by increasing rigidity in the six-membered chelating ring [32]. Indeed, these catalysts... 

Unfunctionalized alkenes have posed more of a problem, as they have no polar moiety which can coordinate to the catalyst. Such an additional metal binding site next to the C = C bond has proven to be crucial for directing coordination to the catalyst and, therefore, rhodium and ruthenium complexes, which are highly selective for functionalized alkenes, generally provide only low enan-tioselectivity for this class of substrates. 

The development of chiral hydrogenation catalysts for unfunctionalized alkenes also allows enantioselective hydrogenation of functionalized olefins where the functionality in the molecule is remote from the double bond. A series of oxazoline-, imidazoline- and pyridine-derived catalysts have been screened for the hydrogenation of unsaturated derivatives of vitamin E (Scheme 30.3). Hy-... 

In addition to the unfunctionalized alkene epoxides discussed in the previous subsection, various other types of epoxides exist that are also derived from unconjugated alkenes but that share two additional features, i. e., being characterized by the presence of one or more functional group(s) and having biological significance. Thus, the present subsection examines epoxy alcohols, epoxy fatty acids, allylbenzenes 2, 3 -oxides, as well as alkene oxide metabolites of a few selected drugs. 

Bridged ethers incorporating stereocontrolled placement of functionality can be prepared by SnCU-induced cyclization of 3,4-epoxy alcohols. A reaction sequence with a ring contraction and tandem cyclization enables the construction, from unfunctionalized alkenes or arenes, of the 8-oxabicyclo[3.2.1]octane system with one or two additional fused rings (Eq. 51) [84]. 

The major drawback of alkene cross-metathesis is the limited ability to control the chemo- and stereoselectivity of the reaction. High yields of the cross-product are obtained by either stoichiometric control or by the use of functionalized alkenes. When unfunctionalized alkenes are used in the reaction, an excess of one of the alkenes must be used in order to get a synthetically useful yield of the... 

The behavior of functionalized alkenes depends strongly on the proximity of the functional group relative to the double bond to be hydroformylated. The few examples described so far reveal that most of the principles used for the hydroformylation of unfunctionalized alkenes can be applied. However, unusual results can be observed with a-functionalized alkenes, i.e., with acrylates. The formation of reactive nonchelated species has been suggested as an explanation of this behavior. Such a phenomenon should probably be generalized to other alkenes bearing functional groups in a suitable position, but experiments still remain to be done under biphasic conditions to confirm this hypothesis. 

Unfunctionalized alkene usually reacts by preferential syn delivery of hydrogen from the less hindered face of the double bond. The degree of stereoselectivity is dependent on the reactant structure, catalysts and reaction conditions. Donor functional groups, particularly hydroxy and amino can be syn directive. 

Hydrogenation is now the most utilized homogeneous catalytic reaction in process chemistry for the synthesis of enantioenriched material. The scope of highly enantioselective hydrogenation is spectacular. It ranges from olefins and ketones functionalized with ligating substituents to unfunctionalized alkenes and ketones. Examples of the asymmetric... 

The most selective - and also most general - titanocene catalyst is complex 35 d, also studied by Buchwald and coworkers. This catalyst was used to hydrogenate a variety of functionalized and unfunctionalized cyclic and acyclic alkenes with excellent ee-values in most cases [46]. Enamines could also be hydrogenated with enantiomeric excesses of 80-90% [47]. However, high catalyst loadings (5-8 mol%) and long reaction times were required to drive the reactions to completion. 

Guided by Marks s report of the samarium-catalyzed hydroboration of alkenes, Molander has developed a samarium-catalyzed protocol for the cyclization/hydroboration of unfunctionalized 1,6-dienes. In an optimized procedure, reaction of 1,5-hexadiene and l,3-dimethyl-l,3-diaza-2-boracyclopentane catalyzed by Gp 2Sm(THF) in toluene at room temperature for 18 h followed by oxidation gave hydroxymethylcyclopentane in 86% yield (Equation (70) R = H, n — ). The transformation was stereoselective, and Sm-catalyzed cyclization/hydroboration of 2-phenyl-1,5-hexadiene followed by oxidation formed /ra/ i--l-hydroxymethyl-2-phenylcyclopentane in 64% yield (Equation (70) R = Ph, n = ). The samarium-catalyzed reactions was also applicable to the synthesis of hydroxymethylcyclohexanes (Equation (70), n=X) but tolerated neither polar functionality nor substitution on the alkenyl carbon atoms. 

Alkanes are the world s most abundant organic resource. Olefins, by contrast, are relatively scarce they are, however, the most important class of intermediate in the commodity chemical industry [1], Thus the ability to convert alkanes to alkenes is a reaction with tremendous potential utility. Likewise, in view of the obvious importance of the carbon-carbon double bond functionality in the synthesis of complex organic molecules, the ability to introduce unsaturation into unfunctionalized alkyl groups is also a very alluring goal. 

Halogenation is a useful tool because it adds a functional group to a previously unfunctionalized molecule, making an alkyl halide. These alkyl halides can then be converted to alkenes by elimination. and to alcohols and ethers by nucleophilic substitution. 

Synthesis of the chiroporphyrins (67) and (68) was achieved by reacting the chiral aldehydes (17 )-(-)-cw-caronaldehyde acid methyl ester and (1/ )-(-)-myrhenal with pyrrole [236]. Chloromanganese(III) derivatives of the Z)2-symmetric a a -atropisomers, which appear to be the most abundant, were applied to the epoxidation of some unfunctionalized aromatic alkenes with PhlO. A high ee value (70%) was obtained in the epoxidation of dihydronaphthalene with this type of catalyst whereas it was significantly lower when functionalized substrates were used (17% for p-chlorostyrene). 

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